Search PubMed⌕ Search

Biomedical subjects

C Nyakas

Publications and source records attributed to C Nyakas.

At least 55 records · Page 3Linked to original sources
PubMed1996

In vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine: combined therapy and temporal course of protection.

Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective potential of this combined drug treatment before and after NMDA-exposure. NMDA was unilaterally injected in the magnocellular nucleus basalis (MBN). Neuronal damage was assessed 12 days after the NMDA-injection by measuring the reduction of cholinergic cortical fibres that originate from the MBN neurons. In controls that received no drug treatment, NMDA-exposure damaged MBN neurons such that 66% of the cholinergic terminals were lost in the ipsilateral parietal cortex. Pretreatment with a nimodipine diet (860 ppm) combined with application of MK-801 (5 mg/kg i.p.) before NMDA-exposure reduced fibre loss by 89% thereby providing a near complete neuroprotection. Combined therapy of MK-801 (5 mg/kg i.p.) and nimodipine (15 mg/kg i.p.) 8 min after NMDA-infusion reduced neuronal injury by 82%, while the same combination given 2 h after the excitotoxic treatment still yielded a 66% protection against neurotoxic damage invoked by NMDA. In conclusion, the present data show that a dual blockade of NMDA-channels and voltage-dependent calcium channels (VDCC's) up to 2 h after NMDA-exposure is able to provide a significant protection against NMDA-neurotoxicity.

Aging↗
PubMed1996

Hypoxia and brain development.

Hypoxia threatens brain function during the entire life-span starting from early fetal age up to senescence. This review compares the short-term, long-term and life-spanning effects of fetal chronic hypoxia and neonatal anoxia on several behavioural paradigms including novelty-induced spontaneous and learning behaviours. Furthermore, it reveals that perinatal hypoxia is an additional threat to neurodegeneration and decline of cognitive and other behaviours during the aging process. Prenatal hypoxia evokes a temporary delay of ingrowth of cholinergic and serotonergic fibres into the hippocampus and neocortex, and causes an enhanced neurodegeneration of 5-HT-ir axons during aging. Neonatal anoxia suppresses hippocampal ChAT activity and up-regulates muscarinic receptor sites for 3H-QNB and 3H-pirenzepine binding in the hippocampus in the early postnatal age. The altered development of axonal arborization and pre- and postsynaptic cholinergic functions may be an important underlying mechanism to explain the behavioural deficits. As far as the cellular mechanisms of perinatal hypoxia is concerned, our primary aim was to study the putative importance of Ca2+ homeostasis of developing neurons by means of pharmacological interventions and by measuring the development of immunoexpression of Ca(2+)-binding proteins. We assessed that nimodipine, an L-type calcium channel blocker, prevented or attenuated the adverse behavioural and neurochemical effects of perinatal hypoxias, while it enhanced the early postnatal development of ir-Ca(2+)-binding proteins. The results are discussed in the context of different related research areas on brain development and hypoxia and ischaemia.

Animals↗
PubMed1996

Long-term selective down-regulation of brain glucocorticoid receptors after neonatal dexamethasone treatment in rats.

The development of corticosteroid receptors may be permanently modified by perinatal hormonal influences. Changes in binding characteristics of corticosteroid receptors were examined in rats treated sc. with 1 microgram/g dexamethasone (DEX) on postnatal day (PND) 1 and subsequently two more times on PND 3 and 5 in several brain areas. [3H]Corticosterone (CORT) binding capacity (Bmax) and affinity (Kd) were determined at 3 weeks old and adult ages by using saturation analysis. The mineralocorticoid type receptor (MR) and the glucocorticoid receptor (GR) sites were measured separately with single point analysis applying a selective glucocorticoid ligand RU 28362 saturating GR. The decrease in CORT binding was due to a selective GR decrement in all structures and the MR concentration was not changed considerably. The basal levels of plasma CORT were not permanently influenced by neonatal DEX. In conclusion, DEX given during the first week of life resulted in long-term and selective down-regulation of GR and this decrement was independent of the actual circulating CORT level.

Animals↗
PubMed1995

Energy homeostasis, autonomic activity and obesity.

Obesity is often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The present paper summarizes the results of a number of studies designed to investigate autonomic functioning in normal, genetically, and experimentally obese rats. Particular emphasis is given to autonomic functioning and dysfunctioning in relation to the processes that are involved in the regulation of peripheral energy substrate homeostasis. It is concluded that alterations in autonomic regulation in obesity are determined by causal factors such as overeating, genetic make-up, age and/or the duration of obesity.

Animals↗
PubMed1995

Cardiac and behavioral responses of long-term obese and lean Zucker rats to emotional stress.

Obesity is known as a risk factor in stress-related cardiovascular pathology in man. The length of obesity can be an important interacting variable. Therefore, cardiac and behavioral responses to emotional stress were studied in 1-year-old, genetically obese (fa/fa) and lean(Fa/-) male Zucker rats, a frequently used animal of genetic obesity. An early bradycardic response to emotional stress evoked by stimuli associated with brief previous inescapable foot shock, as observed in lean rats, was absent in the fatty Zuckers. This difference was not due to a learning deficit: obese and lean Zuckers showed the same degree of conditioned behavioral responses to the emotional stress. Furthermore, the magnitude of the novelty induced behavioral arousal was also comparable. As far as the regulation of body temperature is concerned, the fa/fa rats displayed a diminished increment in rectal temperature in response to the emotional stress. In conclusion, the results showed an impairment of phasic change in the parasympathetic drive of heart to emotional stress in the long-term obese animals. The diminished activation of heat production points to a blunted response of certain branches of the sympathetic nervous system to emotional stress. The findings favor the hypothesis that dysfunction of cardiac vagal drive in relation to stress is of pathologic importance in long-term obesity.

Animals↗
PubMed1995

Effects of early postnatal anoxia on adult learning and emotion in rats.

Cognitive functioning, behavioural attention and anxiety were studied in adult male Wistar rats after early postnatal anoxia. Spatial memory performance in the hole board learning task was impaired in anoxic rats when compared with control animals. Attention assessed by the behavioural immobility response to a sudden reduction in background noise was tested in an open field. In anoxic rats this response was reduced compared to controls, which was further reflected in a higher ambulation score in anoxic animals. The emotional state in adult rats after postnatal anoxia was not affected as was demonstrated in the elevated plus-maze and in the shock probe/defensive burying task. The results indicate that adult cognitive deficits after neonatal anoxia are not related to changes in emotional behaviour. Disruption of behavioural attention or the capacity of concentration to task performance may, however, contribute to the observed cognitive impairment.

Animals↗
PubMed1995

Aldehyde fixation differentially affects distribution of diaphorase activity but not of nitric oxide synthase immunoreactivity in rat brain.

The effect of aldehyde fixation on NADPH- and NADH-dependent diaphorase (d) histochemistry and nitric oxide synthase (NOS) immunocytochemistry in the brain was investigated by comparing the distribution of these enzymes in in situ nitrocellulose blots of unfixed brain sections with that in aldehyde-fixed brain sections. Substitution of NADPH by NADH yielded no gross differences in cellular distribution in the native blot, whereas in fixed sections NADH produced nonspecific staining of the entire section. In the in situ blot NADPHd histochemistry therefore visualized general nitroblue tetrazolium reductase (NBTr) activity, which was particularly strong in hippocampal pyramidal neurons and cerebellar Purkinje cells. Aldehyde fixation abolished the anatomical pattern of general NBTr activity and changed the histochemical distribution in that of the NADPHd activity associated with the distribution of NOS-I immunoreactivity (ir). Fixation intensified NADPHd histochem- ical staining in specific neurons, resulting in outstanding, Golgi-like staining of these neurons in several brain regions, whereas the general NBTr activity in pyramidal and Purkinje cells disappeared. In contrast to the histochemical diaphorase distribution, the distribution of NOS-I ir on blots and in aldehyde-fixed brain sections was similar. No NOS was observed in hippocampal pyramidal and cerebellar Purkinje neurons. In regions like cerebral and cerebellar cortex and striatum the applied anti NOS-I serum had a higher affinity for the native protein. It is concluded that aldehydes, rather than to progressively suppress NOS-unrelated enzymes, differentially elicit NADPHd activity in some groups of neurons while leaving NOS-ir unaffected.

Animals↗
PubMed1995

Neuroprotection against NMDA induced cell death in rat nucleus basalis by Ca2+ antagonist nimodipine, influence of aging and developmental drug treatment.

In the current study the neuroprotective effect of the L-type calcium channel antagonist nimodipine in rat brain was investigated in N-methyl-D-aspartate-induced neuronal degeneration in vivo. In the present model NMDA was unilaterally injected in the magnocellular nucleus basalis and the neurotoxic impact assessed by measuring cortical cholinergic fibre loss as a percentage of fibre density of the intact control hemisphere. This procedure proved to be a reproducible model in which the degree of damage was almost linearly proportional to the NMDA dose. Neuroprotection by nimodipine was determined in a number of conditions. First, the effect of nimodipine treatment in adult animals starting two weeks prior to neurotoxic injury was compared with neuroprotection provided by perinatal treatment of the mother animals with the calcium antagonist. Surprisingly, the degree of protection was in both cases similar, yielding almost 30% reduction of fibre loss. The neuroprotective effect in adulthood of perinatal nimodipine treatment may be explained by developmentally enhanced calcium binding proteins or persistent developmental changes in calcium channel characteristics. Protection by nimodipine was also investigated in aged, 26 month old rats. Compared to young adult cases, aged animals proved to be less vulnerable to NMDA exposure, while nimodipine application was more potent, thus yielding a reduction of nearly 50% in nerve fibre damage induced by NMDA infusions. Possible mechanisms of differential calcium influx in the various experimental conditions will be discussed.

Aging↗
PubMed1994

Induction of enhanced postnatal expression of immunoreactive calbindin-D28k in rat forebrain by the calcium antagonist nimodipine.

The early postnatal development of immunoreactive calbindin-D28k (CaB-ir) containing neuronal systems in hippocampus and parietal cortex was studied in offspring of Wistar rats chronically treated with either the Ca(2+)-channel antagonist nimodipine or placebo food. The drug was applied to the mother animals during the last week of gestation and continued until the end of the experiment. The CaB-ir was investigated in the period of the highest rate of hippocampal and cortical fiber growth at postnatal days (PD), 5, 7, 10 and 20. In the dorsal hippocampus from PD5 to 20, the dentate granule cells and their mossy fiber connection expressed increasing CaB-ir in a topographically organized manner. In the parietal cortex at PD5, 7 and 10 interneurons and a few pyramidal cells gradually appeared immunoreactive for CaB with progressively increasing intensity and approached their adult-like pattern at PD20. Chronic nimodipine treatment resulted in a transient and markedly enhanced ir-CaB expression up to the age of PD10, which was quantified by cell counts and image analysis. Nimodipine induced a more than twofold increase in the number of CaB-ir neurons in the cortex at PD5-PD10. The developmental enhancement in the hippocampus appeared slightly earlier mainly at PD5 and 7. The findings indicate that the antihypoxic effect of nimodipine, previously found in the perinatal age, may be associated with an increased Ca2+ buffering capacity of neurons due to an enhanced expression of ir-CaB during the early postnatal period.

Animals↗
PubMed1994

Life-spanning behavioural and adrenal dysfunction induced by prenatal hypoxia in the rat is prevented by the calcium antagonist nimodipine.

The long-term behavioural effects of prenatal chronic anaemic hypoxia were investigated in young (5 months old), late adult (19 months) and aged Wistar rats (23-26 months). Sodium nitrite (2 g/l) offered in the drinking water during the second half of pregnancy served to evoke prenatal hypoxia. In parallel to nitrite treatment the Ca2+ channel blocker nimodipine (10 mg/kg) or vehicle alone was administered intragastrically once daily. Open-field activity, intermale social behaviour, learning ability in a black-white discrimination paradigm and fear-induced emotionality were assessed at different ages. Plasma corticosterone response to novelty stress was measured by blood sampling through chronic venous canulas at the age of 28 months. The nitrite-exposed 5-month-old offspring started exploration in a novel open-field with considerable delay. This delayed start-latency was augmented in 19- and 23-month-old rats, pointing to exaggerated suppression of behavioural arousal. Nitrite-induced hypoxia decreased the duration of social interactions during ageing. Aged rats exposed to nitrite were unable to learn a black-white discrimination but showed a normal generalized conditioned fear response (immobility) to the test situation as a whole. The conditioned fear-induced vocalization was more frequent among hypoxic aged animals. The aged hypoxic rats displayed a prolonged plasma corticosterone stress response and had higher adrenal weight than their controls. The abnormal open-field, social, learning and emotional behaviours, as well as the altered plasma corticosterone response, were prevented by prenatal nimodipine treatment.

Adrenal Insufficiency↗
PubMed1994

Nimodipine accelerates the postnatal development of parvalbumin and S-100 beta immunoreactivity in the rat brain.

The effects of chronic maternal perinatal nimodipine treatment on the immunocytochemical distribution of the Ca(2+)-binding proteins parvalbumin (PV) and S-100 beta in neocortex and hippocampus were studied at the age of postnatal day (PD) 5, 7, 10, 14 and 20. The Ca2+ antagonist nimodipine (1000 ppm BAY e 9736 in daily food) was administered to pregnant rats starting at postconceptual day 11. The expression of PV exemplified in layer V of parietal and retrosplenial cortex and in all hippocampal layers of CA1 and CA3 was enhanced by more than two-fold in the offspring of nimodipine-treated dams at PD 10 compared with placebo-treated animals. The difference was no longer present at PD 14 and 20. Nimodipine administration also significantly increased the number of S-100 beta-immunopositive glial cells in upper neocortical layers I-III at PD 5 and 7. Again, the difference between nimodipine and placebo-treated animals disappeared after PD 10. The data indicate an accelerated development of PV and S-100 immunoreactivity in the postnatal forebrain as a result of perinatal blockade of the L-type Ca2+ current.

Aging↗
PubMed1994

Postnatal development of hippocampal and neocortical cholinergic and serotonergic innervation in rat: effects of nitrite-induced prenatal hypoxia and nimodipine treatment.

Postnatal development of ingrowing cholinergic and serotonergic fiber patterns were studied in the rat hippocampus and parietal cortex employing a histochemical procedure for acetylcholinesterase as a cholinergic fiber marker, and immunocytochemistry of serotonin for serotonergic fiber staining. The rat pups were killed at postnatal days 1, 3, 5, 7, 10, and 20. The development of cholinergic and serotonergic innervation was described and the fiber density quantified under normal conditions and after long-term prenatal anemic hypoxia induced by chronic exposure to sodium nitrite. Furthermore, a third group was studied in which the nitrite hypoxia was combined with a simultaneous treatment with the Ca(2+)-entry blocker nimodipine to test the neuroprotective potential of this drug. Quantitative measurement of fiber density from postnatal day 1 to day 20 yielded the following results: (i) both neurotransmitter systems revealed an age-dependent and an anatomically-organized developmental pattern; (ii) the serotonergic innervation of the dorsal hippocampus preceded that of cholinergic afferentation in postnatal days 1-3; (iii) prenatal hypoxia induced a transient delay in the innervation of parietal neocortex and dentate gyrus for both neurotransmitter systems, but left the innervation of the cornu ammonis unaffected; and (iv) the hypoxia-induced retardation of cholinergic and serotonergic fiber development was prevented by concomitant application of the Ca(2+)-antagonist nimodipine during the hypoxia. The results indicate that prenatal hypoxia evokes a temporary delay in the cholinergic and serotonergic fiber outgrowth in cortical target areas in a region-specific manner. The hypoxia-induced growth inhibition is prevented by the calcium antagonist nimodipine, which supports the importance of the intracellular Ca2+ homeostasis of cells and growth cones in regulating axonal proliferation.

Acetylcholinesterase↗
PubMed1993

Behavioral depression: opposite effects of neonatal dexamethasone and ACTH-(4-9) analogue (ORG 2766) treatments in the rat.

Permanent changes in novelty-induced arousal and behavioral depression were studied in adult male Wistar rats having received sc injections of 1 micrograms/g body wt dexamethasone (DEX) or ACTH-(4-9) analogue (ORG 2766), or the combined treatment of these substances at Postnatal Days 1, 3, and 5. Treatment with DEX increased immobility in the Porsolt's water immersion and closed-field tests, delayed start latency, and attenuated orientation motility in an open-field, and enhanced defensive burying activity. On the contrary, the ACTH peptide caused more active behavior, resulted in an increased motility in the Porsolt's test, and decreased immobility in the closed-field chamber compared to controls. Behavioral reactivity of rats after combined DEX and ACTH peptide treatments was comparable to that of saline controls. The hormone treatments did not alter basal and stress-induced circulating corticosterone levels assessed at the adult age. The data suggest that neonatal DEX strengthens the development of brain mechanisms supporting behavioral depression in response to stressful situations, while ORG 2766 has principally an opposite effect and is able to compensate the long-term aberrant behavioral effects of neonatal DEX treatment.

Adrenocorticotropic Hormone↗
PubMed1993

Neuroendocrine and behavioral effects of vasopressin in resting and mild stress conditions.

Neuroendocrine and behavioral effects of subcutaneously administered AVP (6 micrograms/kg b.wt.) were determined in resting conditions and after the mild stress of transportation to and placement in a novel environment. In resting conditions, systemic administration of AVP caused a rapid increase in blood glucose level and a long-lasting increase in CORT secretion. A decrease in circulating plasma NE level was observed. AVP did not affect adrenal medullary E secretion. The stress-induced sympathetic activation, as reflected in plasma NE level, was inhibited 60 min after AVP administration. Stress-induced increases in blood glucose, CORT, and E secretion were not influenced by AVP. In resting condition, AVP caused a 60-min lasting increase in grooming behavior with a concomitant decrease in time spent resting. Sixty minutes after administration, the behavioral activation after the stress of transportation and placement in a novel environment was more rapidly terminated in AVP-treated rats than in vehicle-treated control rats. The state- and time-dependent modulation of spontaneous behavior suggests that AVP has arousing properties shortly after administration when marked pressor and endocrine effects are apparent. In a later phase, AVP may facilitate dearousal mechanisms following stress-induced behavioral activation.

Animals↗
PubMed1993

In situ blotting: a novel method for direct transfer of native proteins from sectioned tissue to blotting membrane: procedure and some applications.

We describe a novel technique for direct transfer of native proteins from unfixed frozen tissues sections to an immobilizing matrix, e.g., nitrocellulose, polyvinyliden difluoride, or positively charged nylon membranes. Proteins are directly blotted onto the membrane, providing optimal accessibility for molecular detection but retaining the anatomic localization at the cellular level. Within 10 min a maximum protein transfer is achieved independent of the protein molecular weight. The total protein bound was 80% of the maximal binding capacity of the blotting membrane and independent of the section thickness. These results indicate that the proteins that bind to the membrane originate from the cut cell monolayer that has direct contact with the blotting membrane. This in situ blotting method provides direct protein mapping from a single cell layer of a tissue section. The procedure includes cryosectioning at 20 microns and collecting sections on a dry blotting membrane at -20 degrees C. For protein transfer the blotted sections are thawed and incubated for 10 min with Tris buffer. After incubation the sections are removed from the membrane by high-pressure spray. The blotted membranes can be subjected to several detection assays. In the present study the presence of several proteins was demonstrated in brain and thymus by immunochemical and enzyme histochemical procedures.

Animals↗
PubMed1992

Behavioral and cardiac responses after intracerebroventricular corticotropin-releasing hormone (CRH) administration: role of adrenal cortical hormones.

Intracerebroventricularly (icv) administered corticotropin-releasing hormone (CRH) produces a dose-dependent increase in heart rate in association with behavioral activation. The present study was designed to investigate whether these CRH-induced responses are dependent on adrenal function. The effects of adrenalectomy (ADX) and subsequent corticosterone replacement were studied. Administration icv of 300 ng of CRH failed to produce behavioral activation and tachycardia in ADX rats. Corticosterone replacement restored the CRH-induced behavioral response to preoperative levels, whereas the CRH-induced tachycardia was partially restored. This latter result may be related to the fact that the baseline heart rate of ADX animals appeared to be significantly higher than that of corticosterone-treated ADX animals. It is concluded that circulating adrenal corticosterone in ADX rats is involved in the expression of the behavioral and cardiac effect of central CRH.

Adrenal Cortex Hormones↗
PubMed1992

Vasopressin prolongs behavioral and cardiac responses to mild stress in young but not in aged rats.

In young male Wistar rats sudden silence superimposed on low intensity background noise evokes a relative decrease in heart rate. This bradycardia is accompanied by immobility behavior. In the present study, involving young (3 month), late-adult (14 month), aged (20 month), and senescent (25 month) rats the magnitude of the stress-induced bradycardia shows an age-related reduction while the behavioral immobility response remained unchanged during the process of aging. Arginine-8-vasopressin (AVP, 6 micrograms/kg SC) administered 60 min prior to the experiment led to a prolonged behavioral and cardiac stress response in young and late-adult rats, but not in aged and senescent animals. The peripheral and central mechanisms possibly involved in the failure of systemically applied AVP to improve bradycardiac stress responses in aged rats are discussed.

Aging↗